LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas

Orsolya Rusz, Orsolya Papp, Laura Vizkeleti, Bela Akos Molnar, Kristof Csaba Bende, Gabor Lotz, Balazs Acs, Zsuzsanna Kahan, Tamas Szekely, Agnes Bathori, Csilla Szundi, Janina Kulka, Zoltan Imre Szallasi, Anna-Maria Tokes*

*Corresponding author for this work

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    To determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas.Two cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.5% of patients). (2) Tissue microarray (TMA) of 74 HR-breast carcinomas treated with adjuvant therapy (77.0% of the patients received anthracycline, 17.6% of the patients non-anthracycline-based therapy, and in 5.4% of the cases, no treatment data are available). Interphase FISH technique was applied on pretreatment core biopsies (cohort I) and on TMAs (cohort II) using custom-made dual-labelled FISH probes (LAPTM4B/CEN8q FISH probe Abnova Corp.).In the neoadjuvant cohort in the anthracycline-treated group, we observed a significant difference (p = 0.029) of average LAPTM4B copy number between the non-responder and pathological complete responder groups (4.1 +/- 1.1 vs. 2.6 +/- 0.1). In the adjuvant setting, the anthracycline-treated group of metastatic breast carcinomas was characterized by higher LAPTM4B copy number comparing to the non-metastatic ones (p = 0.046). In contrast, in the non-anthracycline-treated group of patients, we did not find any LAPTM4B gene copy number differences between responder vs. non-responder groups or between metastatic vs. non-metastatic groups.Our results confirm the possible role of the LAPTM4B gene in anthracycline resistance in HR- breast cancer. Analyzing LAPTM4B copy number pattern may support future treatment decision.
    Original languageEnglish
    JournalCancer Chemotherapy and Pharmacology
    Pages (from-to)139-147
    Publication statusPublished - 2018


    • Breast carcinomas
    • LAPTM4B
    • Anthracycline-based chemotherapy
    • FISH

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